Advances in genomics have the potential to improve the delivery of health care by targeting interventions to individuals who will receive the greatest benefit and experience the lowest risk of adverse events. More effective targeting of interventions is particularly appealing because it is one of the few approaches that can both improve outcomes and reduce costs- the unquestioned sweet spot of health care reform. However, genomic medicine has a long way to go before it gets to that sweet spot. Some of what is needed is discovery of gene-disease associations that lead to the development of a clinical genetic test. But increasingly, the needs lie not in developing the test but in deciding whether using the test is better than doing what we are currently doing - i.e. comparative effectiveness. The overarching goal of this project is to develop a coordinated, multidisciplinary center for the generation and synthesis of evidence to support the translation of genomic tests into improvements in cancer prevention, screening, diagnosis, treatment and survivorship. The center (entitled the Center for Comparative Effectiveness in Genomic Medicine or CCEGM) will involve two primary scientific components: (1) evidence generation;and (2) evidence synthesis and modeling. The goal of the evidence generation component is to conduct observational and experimental studies of the comparative effectiveness of genomic test that are clinically available or nearly clinically available. Four proof of principle, pilot studies are included in this proposal: (1) pharmacogenomics of nicotine addiction treatment;(2) incremental information from breast cancer SNP panels in breast cancer risk screening and prevention;(3) personalized treatment for non small cell lung cancer;and (4) CDKN2A/p16 testing and adherence to melanoma prevention behaviors. The goal of the evidence synthesis component is to use statistical and modeling methods to bring together existing evidence to inform recommendations about clinical practice. Three corresponding evidence synthesis pilot projects are included: a systematic review of the clinical validity of EGFr and K-ras mutations in predicting response to treatment, a decision model of the use of SNP panels in breast cancer screening, a cost- effectiveness model of nicotine metabolism markers in treatment of nicotine addiction. PUBLIC HEALTH RELEVANCE: Advances in genomics have the potential to improve the delivery of health care. Increasingly, there is a need to decide whether the use of genomic tests is better than doing what we are currently doing - i.e. comparative effectiveness. The overarching goal of this project is to develop a coordinated, multidisciplinary center for the generation and synthesis of evidence to support the translation of genomic tests into improvements in cancer prevention, screening, diagnosis, treatment and survivorship.